Podcast Summary: Derms on Drugs

Episode: "Tissue Issues: A Deep Dive into Cutaneous Connective Tissue Disease"

Date: March 6, 2026
Host(s): Matt Zirwas, Laura Ferris, Tim Patton
Guest: Dr. Lauren Graham (University of Alabama, Birmingham)

Overview

This episode offers a dynamic, in-depth exploration of cutaneous connective tissue diseases, focusing especially on cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). The hosts, joined by special guest and connective tissue expert Dr. Lauren Graham, dissect the latest research, evolving therapies, diagnostic challenges, disease scoring, and more. The tone is lively, fun, slightly irreverent, and loaded with useful clinical pearls for dermatology professionals.

Key Discussion Points and Insights

1. Dr. Graham’s Path to Connective Tissue Disease (01:13)

• Dr. Graham shares her journey: from an MD/PhD in collagen research at UAB, to a residency at Northwestern, sparking her interest through exposure to combined clinics (lupus, scleroderma, psoriasis/psoriatic arthritis).
• Quote: “I did my PhD work on collagen regulation… tried a derm rotation in third year and really liked it… fell in love with connective tissue disease.” (01:25–03:02)

2. Review of Ducravacitinib in Cutaneous Lupus (04:22)

Paper: Autoimmunity Reviews: “Ducravacitinib: Superior efficacy and safety in Cutaneous Lupus erythematosus compared to various biologics and small molecules: Systematic review and meta-analysis.”
Presenter: Dr. Laura Ferris

Core Findings

• Ducravacitinib (a TIC2 inhibitor, not FDA-approved for CLE) appears more effective than ustekinumab and baricitinib, based on odds of achieving CLASI-50 improvement.
  • Odds ratios: Ducravacitinib 8.28, lidifilimab 2.54, anafrolumab 2.25 (vs placebo) (08:18).
• Only one true phase 2 RCT with 218 SLE patients (multiple dosing arms) informs ducravacitinib's strong showing; overall study quality varies.
• CLASI (Cutaneous Lupus Area and Severity Index)—A score of 50% improvement (“CLASI-50”) defines clinical response, but meaningfulness is relative to baseline severity.
  • “If they’re really bad, 50 percent better is a decent amount. The standard is that 50% change is clinically significant.” —Dr. Graham (09:27)

Safety

• No higher overall adverse event rates for ducravacitinib vs placebo.
• Baricitinib showed higher SAEs.

Industry Insight

• Matt: “It’s like they (BMS) don’t want to make any money… they never did a lupus study, never did atopic derm. Who’s running their pipeline?” (15:12)

Clinical Takeaways

• Ducravacitinib is used off-label by some (difficult approval, occasional success), “We’re in an exciting time for skin lupus, still.” —Dr. Graham (20:39)
• “We have so much need for something that’s easy to use and relatively safe.” —Dr. Ferris (16:14)
• Hydroxychloroquine sometimes triggers psoriatic dermatitis, a nuance in coverage/diagnosis.

3. Litifilimab for Cutaneous Lupus: The LILAC Study (21:52)

Paper: Morola et al. “Litifilimab efficacy on skin outcomes in cutaneous lupus erythematosus: Phase 2 LILAC study”

Mechanism and Background

• Anti-BDCA2 monoclonal antibody, it inhibits PDCs and downstream type 1 interferon signaling; promising for CLE.

Results

• Fast Results: Statistically significant improvement at Week 4 for CLASI-50 at top dose; 70% on best dose vs 17% on placebo.
• Placebo group improvement often reflects better compliance with background therapy during trials, per Dr. Patton and Dr. Graham.
• Works especially well for higher baseline disease activity.

Safety & Practice Insights

• No alarming safety signals for litifilimab; less concern for viral infections compared to anafrolumab.
• “It works fast, and they saw a difference at week 4, which is exciting.” —Dr. Graham (25:40)
• Subjective improvement: Physician global impression aligns with how dermatologists practice (“Are you better, worse, or the same?”), even though it’s subjective.

4. Anafrolumab in SLE/CLE (39:00)

• Good real-world results: Used increasingly in SLE patients with poorly controlled skin disease; “The first thing we’re giving them is anafrolumab. And it works really well and it works fast.” —Dr. Graham (40:00)
• Infectious risk (particularly herpes zoster); zoster vaccination recommended before use.
• Subcutaneous formulation in EU (approved December 2025), with trials ongoing in the US.

Clinical Pearl

• Use of systemic lupus diagnosis can facilitate access to advanced therapies for severe CLE.

5. Diagnostic Pearls and New Developments

• No major new diagnostic labs for lupus or DM—clinical evaluation is still paramount.
• Dr. Graham: “The biggest thing is just recognizing the difference between lupus and dermatomyositis… Do a good clinical exam. Make sure it’s not dermato.” (46:25)

6. Dermatomyositis: New and Old Treatments (48:30)

• Therapies: IVIG (only FDA-approved), methotrexate, mycophenolate, increasing off-label JAK inhibitor usage (tofacitinib, upadacitinib); repicitinib (TIC2/JAK1) in phase 3 trials.
• Oral Roflumilast: Emerging as a promising therapy for cutaneous DM (anecdotal use by Dr. Zirwas).
• IVIG: Good for skin, not perfect—may be less effective for complete clearance.
• Cancer Screening: Follow new guidelines—comprehensive annual screening for at least first 3 years after DM diagnosis.
• Myositis Antibody Panels: Utility is there, but false negatives are common and treatment shouldn’t wait for results.

7. Clinical Pattern Recognition in Dermatomyositis (56:42)

• Teaching pearls: Examine recalcitrant scalp erythema, violaceous upper back/arms, Gottron's papules (knuckles); heliotrope is overrated.
• “The upper back and outer arms, a little bit violaceousy—that’s my bells ringing for DM.” —Dr. Zirwas (57:29)

Notable Quotes & Memorable Moments

• “My job is to be like our listeners who didn’t look anything up ahead of time, so I gotta ask the questions they would ask. Plus it’s a good excuse for me to do less work.” – Matt (11:08)
• “If you're describing yourself as classy, you're not.” – Matt, playing on the CLASI acronym (12:07)
• “We used to have nothing—literally it was Plaquenil, maybe quinacrine, methotrexate, and that was it.” – Dr. Zirwas on historic lupus management (21:15)
• “Nothing is FDA-approved for cutaneous lupus as a standalone disease, and as derms, we see that fairly frequently.” – Dr. Patton (22:12)
• “I do all cancer screening yearly for three years” after DM diagnosis – Dr. Graham (53:26)
• “Heliotrope is one of the most overhyped signs—I identify it after I know they have dermato.” – Matt (58:17)
• “If anything, this tells us we need to own cutaneous lupus… if we do get things FDA approved, dermatologists really need to be empowered.” – Dr. Graham (45:28)

Timestamps for Important Segments

• Dr. Graham’s background & training: 01:13–03:02
• Ducravacitinib review, CLASI-50 explanation: 04:22–10:49
• Meta-analysis results (odds ratios): 08:18–12:07
• Litifilimab (LILAC study), trial setup: 21:52–30:02
• Discussion of disease scoring (CLASI, physician's global impression): 29:51–34:47
• Anafrolumab in SLE/CLE: 39:00–44:14
• Accessing advanced therapies via SLE diagnosis: 44:14–45:28
• New developments in diagnosis: 46:25–46:41
• Dermatomyositis therapies (IVIG, JAKs, repicitinib): 48:51–52:18
• Malignancy screening in DM: 53:05–54:15
• Dermatomyositis antibody panels and diagnosis: 54:58–56:39
• Clinical pattern recognition for DM: 57:29–58:43

Trivia & Historical Nuggets (59:32–65:27)

• First use of antimalarials for SLE noted in World War II soldiers on malaria prophylaxis.
• ANA testing uses the HeLa cell line rather than the original Hep-2.
• Gottron (of Gottron papules fame) took over after a Jewish dermatologist (Jessner, of Jessner's peel) was ousted during Nazi era.

Conclusion

The episode is equal parts clinical review and comedic banter, offering:

• Up-to-the-minute discussion on the latest therapeutics for cutaneous lupus and dermatomyositis (Ducravacitinib, litifilimab, anafrolumab, IVIG, oral refulmilast).
• Real-world insights from an expert with nuanced, honest discussion of what actually works in clinic.
• Practical pearls on scoring, diagnosis, and recognizing disease patterns.
• Engaging anecdotes and discussion on the path to new drug approvals, real-world barriers, and employing "creative" diagnoses to unlock needed therapies.

Perfect for dermatology clinicians eager for lively, actionable updates in connective tissue disease.

“We’re in an exciting time for skin lupus... I hope dermatologists are empowered to take care of these patients.”
— Dr. Lauren Graham (45:33)